Control of the cytotoxicity of dansylated polytheonamide mimic,an artificial peptide ion channel,by modification of the N-terminal structure |
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Authors: | Hiroaki Itoh Shoko MatsutakaTakefumi Kuranaga Masayuki Inoue |
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Affiliation: | Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan |
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Abstract: | We demonstrate that the cytotoxicity of dansylated polytheonamide mimic (2) is controlled by chemical modification of its N-terminal structure. Dansylated polytheonamide mimic (2) is an ion channel peptide which displays potent cytotoxicity against P388 mouse leukemia cells (IC50 = 12 nM). To modulate its cytotoxicity, three analogues of 2, possessing distinct N-terminal structures with different hydrophobicities, were synthesized and their cytotoxicities were evaluated. This focused structure–activity relationship study unveiled that the cytotoxicity of 2 is enhanced 10-fold by simply changing its N-terminal 5,5-dimethyl-2-oxohexanamide to the more hydrophobic palmitamide. The data obtained here provide new understanding for the functional control of the artificial ion channel peptide 2. |
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Keywords: | Cytotoxic agents Natural products Structure&ndash activity relationships Peptides |
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